Genome Rearrangements, Deletions, and Amplifications in the Natural Population of Bartonella henselae

Abstract

Cats are the natural host for Bartonella henselae, an opportunistic human pathogen and the agent of cat scratch disease. Here, we have analyzed the natural variation in gene content and genome structure of 38 Bartonella henselae strains isolated from cats and humans by comparative genome hybridizations to microarrays and probe hybridizations to pulsed-field gel electrophoresis (PFGE) blots. The variation in gene content was modest and confined to the prophage and the genomic islands, whereas the PFGE analyses indicated extensive rearrangements across the terminus of replication with breakpoints in areas of the genomic islands. We observed no difference in gene content or structure between feline and human strains. Rather, the results suggest multiple sources of human infection from feline B. henselae strains of diverse genotypes. Additionally, the microarray hybridizations revealed DNA amplification in some strains in the so-called chromosome II-like region. The amplified segments were centered at a position corresponding to a putative phage replication initiation site and increased in size with the duration of cultivation. We hypothesize that the variable gene pool in the B. henselae population plays an important role in the establishment of long-term persistent infection in the natural host by promoting antigenic variation and escape from the host immune response.

Multilocus Sequence Typing of Bartonella henselae in the United Kingdom Indicates that Only a Few, Uncommon Sequence Types Are Associated with Zoonotic Disease

“…1). Comparison of allelic profiles of STs using eBURST resulted in the three new STs being assigned to one of the three previously described CCs within the species (1,15,20,22,29) (see Fig. S3 in the supplemental material).…”

“…To determine how the population structure of B. henselae in domestic cats (i.e., the natural reservoir) in England fits with that on a wider geographical scale, data from previous MLST studies (1,15,20,22,29) were collated and divided into three categories, i.e., United Kingdom, continental Europe, and the rest of the world (Table 3). The distributions of the common STs in these three categories were not random; ST1 and ST5 were significantly more common in countries outside Europe than in England, and ST5 and ST7 was significantly more common in continental Europe than in England.…”

“…Why these three STs, and not ST1, present the greatest public health risk in the United Kingdom is unclear; however, given that geography is a determinant of B. henselae population structure, it is not an unsurprising observation. It is noteworthy that the vast majority of human-associated isolates included in earlier MLST studies were not from Western Europe (1,15,20,22,29), and the worldwide zoonotic importance of ST1 was determined using univariant analysis without considering geographic influence. Thus, whereas B. henselae strains belonging to ST1 may be more likely to be associated with zoonosis in Australia, Japan, and maybe the United States, this association does not necessarily hold elsewhere, as demonstrated in our study.…”

“…Alignment of verified sequences was carried out using MEGA V4.0 (27). Alleles and STs were assigned in accordance with published data (1,15,20,22,29). New allelic combinations were assigned to new STs in their order of detection.…”

“…A study in the Netherlands, based on comparison of 16S rRNA gene sequences, provided the first evidence that B. henselae strains possessing a particular genotype were more frequently associated with zoonosis than others (5). Further support for this observation has resulted from the use of multilocus sequence typing (MLST) (1,15,20). The first application of MLST to B. henselae involved 37 feline and human isolates and identified seven sequence types (STs) that formed three deeprooted lineages, termed clonal complexes (CCs), within the species (15).…”